Synthesis and use of oxa-spirodiphosphine ligand

ABSTRACT

The present invention relates to the technical field of chiral synthesis, and specifically provides a new type of oxa-spirodiphosphine ligands. The bisphosphine ligand is prepared with oxa-spirobisphenol as a starting material after triflation, palladium catalyzed coupling with diaryl phosphine oxide, reduction of trichlorosilane, further palladium catalyzed coupling with diaryl phosphine oxide, and further reduction of trichlorosilane. The oxa-spiro compound has central chirality, and thus includes L-oxa-spirodiphosphine ligand and R-oxa-spirodiphosphine ligand. The racemic spirodiphosphine ligand is capable of being synthesized from racemic oxa-spirobisphenol as a raw material. The present invention can be used as a chiral ligand in the asymmetric hydrogenation of unsaturated carboxylic adds. The complex of the ligand with ruthenium can achieve an enantioselectivity of greater than 99% in the asymmetric hydrogenation of methyl-cinnamic acid.

TECHNICAL FIELD

The present invention relates to the field of asymmetric catalysis, andparticularly to the synthesis of a novel oxa-spirodiphosphine ligand.The compound can be used as a chiral ligand in asymmetric catalyticreactions and has high potential of use in the field of asymmetriccatalysis.

BACKGROUND

In the past few decades, asymmetric catalysis has achieved rapiddevelopment. Various chiral ligands have been synthesized and used inthe field of asymmetric catalysis. Among numerous chiral ligands, thediphosphine ligand is one of the ligands that are most widely used andextensively studied so far. It exhibits excellent activity andenantioselectivity in asymmetric hydrogenation, asymmetrichydroformylation, asymmetric Pauson-Khand reaction, asymmetric Heckreaction, asymmetric cycloaddition reaction, and asymmetriccycloisomerisation reaction, etc.

DIOP synthesized by the Kagan's team, BINAP developed by the Noyori'steam, and DIPAMP ligand developed by the Knowles' team are milestones inthe development history of diphosphine ligands. They have been widelyused in academia and industry. Then various chiral diphosphine ligandswere synthesized, for example, SegePhos, DifluoPhos, SynPhos,C_(n)-TunePhos, TangPhos, DuanPhos, ZhangPhos, SKP, SDP, and SFDP.

Although chiral diphosphine ligands are now very rich in both types andnumbers, each ligand has its unique properties. Therefore, thedevelopment of new chiral diphosphine ligands is of great importance.

SUMMARY

In view of the problems needed to be overcome in the prior art, thepresent invention provides an oxa-spirodiphosphine ligand having astructure of general Formula (I) below:

where in general Formula (I): R¹ and R² are independently alkyl, alkoxy,aryl, aryloxy, or hydrogen, in which R¹, R², R³ and R⁴ may or may notform a ring; R¹ and R⁶ are independently alkyl, aryl, or hydrogen; andR¹ and R⁸ are alkyl, benzyl, or aryl.

The term alkyl is preferably methyl, ethyl, propyl, butyl, or the like.

The term alkoxy is preferably methoxy, ethoxy, propoxy, butoxy, or thelike.

The aryl is preferably phenyl that is unsubstituted or substituted withalkyl or alkoxy as defined above.

The aryloxy is preferably methoxyphenyl, ethoxyphenyl or the like.

Further preferably, R¹, R², R³, R⁴, R⁵, and R⁶ are all hydrogen.

The oxa-spirodiphosphine ligand is the (±)-oxa-spirodiphosphine ligand,the (+)-oxa-spirodiphosphine ligand, or the (−)-oxa-spirodiphosphineligand.

In a further preferred embodiment, the oxa-spirodiphosphine ligand is acompound having a structure below:

in which, preferably, Ar is alkyl, benzyl or aryl; and most preferablyAr is phenyl, or phenyl substituted with alkyl or alkoxy.

The alkyl and alkoxy are as defined above.

Another object of the present invention is to provide a method forsynthesizing the compound by the following route:

Another object of the present invention is to provide use of thecompound in catalyzing asymmetric reactions including hydrogenationreaction, hydroformylation reaction, hydrosilation reaction,hydroboration reaction, hydroxylation with hydrogen peroxide,hydroamination reaction, hydrocyanation reaction, isomerization andformylation reaction, hydroaminomethylation reaction, transferhydrogenation reaction, allylation reaction, olefin metathesis reaction,cycloisomerization reaction, Diels-Alder reaction, asymmetric couplingreaction, Aldol reaction, Michael addition reaction, asymmetricepoxidation reaction, kinetic resolution and [m+n] cyclization reaction.

The diphosphine ruthenium acetate complex prepared from the compound hasa high activity and an enantioselectivity of greater than 99% for thehydrogenation of unsaturated carboxylic acids in organic solvents.

The diphosphine ruthenium acetate complex is a compound having astructure below:

where R=alkyl, fluoroalkyl or aryl; and alkyl and aryl as defined aboveare preferred.

Specifically, in a preferred catalytic asymmetric reaction, the compoundis used as a catalyst, and the reaction route is as follows:

R=alkyl, fluoroalkyl or aryl; and preferably alkyl and aryl as definedabove.

Another object of the present invention is to provide a bisphosphineruthenium acetate complex, which has high activity andenantioselectivity for hydrogenation of unsaturated carboxylic acids inan organic solvent. The bisphosphine ruthenium acetate complex is acompound shown below:

where R=alkyl, fluoroalkyl or aryl; and alkyl or aryl as defined aboveare preferred.

Compared with the prior art, the present application has the followingbeneficial effects.

(1) The oxa-spiro compound has central chirality, and thus includeL-oxa-spirodiphosphine ligand and R-oxa-spirodiphosphine ligand. Theracemic spirodiphosphine ligand can be synthesized from racemicoxa-spirobisphenol as a raw material.

(2) The present invention can be used as a chiral ligand in theasymmetric hydrogenation of unsaturated carboxylic acids. Its complexwith ruthenium can achieve an enantioselectivity of greater than 99% inthe asymmetric hydrogenation of methyl-cinnamic acid.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic view showing the preparation of various chiralcompounds according to the present invention, and the correspondingconversion rates and enantioselectivity ee.

DESCRIPTION OF THE EMBODIMENTS

The present invention will be described below by way of examples withreference to accompanying drawings. However, the present invention isnot limited thereto.

Example 1 Synthesis of(R)-2-H,2′-H-3,3′-spirobi[benzofuran]-4,4′-di(trifluoromethanesulfonate)2

Under a N₂ atmosphere, (S)-6 (7.68 g, 30 mmol) was added to a 250 mLreaction flask, and then dry dichloromethane (150 mL) was added.Pyridine (6.0 mL, 100 mmol) was added with stirring at room temperature.After the reaction system became clear, it was cooled to 0° C., and thenTf₂O (12.0 mL, 70 mmol) was added dropwise. After that, the reactionsystem was warmed to room temperature and continuously stirred for 1 h.The reaction was quenched with water. The reaction system was washedwith dilute hydrochloric acid, and the organic phase was removed of thesolvent under reduced pressure, and then purified by columnchromatography to obtain the product (S)-7 (15.6 g, yield: 99%)

White solid. ¹H NMR (500 MHz, CDCl₃) δ 4.70 (d, J=10.0 Hz, 2H, CH₂),4.87-4.90 (m, 2H, CH₂), 6.91-6.93 (m, 4H, Ar), 7.32 (dd, J₁=8.5 Hz,J₂=8.0 Hz, 2H, Ar). ¹³C {1H} NMR (126 MHz, CDCl₃) δ 162.3, 145.8, 131.9,119.8, 118.1 (q, J=320.0 Hz, CF₃), 113.1, 110.4, 82.5, 54.9. ¹⁹C {1H}NMR (126 MHz, CDCl₃) δ −74.23. HRMS (ESI) calcd. for C₁₇1H₁F₆O₈S₂[M+H]⁺: 520.9800, Found: 520.9794, [α]²⁰ _(D)=+19.2 (c=0.5, acetone).

Example 2 Synthesis of (R)-4′-(diphenylphosphineoxide)-2H,2′H-3,3′-spirobi[benzofuran]-4-trifluoromethanesulfonate 3a

Under a N₂ atmosphere, 2 (5.2 g, 10 mmol), dppb (213 mg, 0.05 mmol),Ph₂POH (3.87 g, 15 mmol), Pd(PAc)₂ (112 mg, 0.05 mmol), and DIPEA (6.5mL, 40 mmol) were added to a reaction flask, and finally DMSO (50 mL)containing no water and oxygen was added. The reaction was continued at100° C. for 6 h. After cooling to room temperature, water was added toquench the reaction, and the reaction system was extracted with ethylacetate. The organic phase was dried over anhydrous sodium sulfate,removed of the solvent under reduced pressure, and simply purified bycolumn chromatography to obtain the product 3a (5.15 g, yield=90%).

White solid. ¹H NMR (400 MHz, CDCl₃) δ 4.64-4.68 (m, 2H, CH₂), 4.77 (d,J=9.6 Hz, 1H, CH₂), 5.15-5.18 (m, 1H, CH₂), 6.40 (d, J=8.0 Hz, 1H, Ar),6.58-6.60 (m, 1H, Ar), 6.78-6.80 (m, 1H, Ar), 6.88-6.90 (m, 1H, Ar),6.94-6.98 (m, 2H, Ar), 7.05-7.13 (m, 3H, Ar), 7.16-7.20 (m, 2H, Ar),7.24-7.28 (m, 4H, Ar). ¹³C {1H} NMR (101 MHz, CDCl₃) δ 162.6, 160.3,145.4, 136.6, 134.5, 133.4 (m), 132.3, 132.0, 131.2, 130.0, 128.4 (m),122.6 (m), 120.7, 112.3, 110.9, 109.4, 84.5, 82.9, 56.3, 26.9. ³¹P {1H}NMR (202 MHz, CDCl₃) δ 21.95 (s). HRMS (ESI) calcd. for C₁₈H₂₁O₆F₃PS[M+H]⁺: 573.0749, Found: 573.0743, [α]²⁰ _(D)=+237.2 (c=0.5, acetone).

Example 3 Synthesis of(R)-4′-(diphenylphosphine)-2H,2′H-3,3′-spirobi[benzofuran]-4-trifluoromethanesulfonate4a

In a 100 mL sealed tube, 3a (2.86 g, 5 mmol), DIPEA (6.6 mL, 40 mmol),20 mL, and trichlorosilane (2.0 mL, 20 mmol) were added. The reactionwas stirred overnight at 120° C. The reaction system was quenched withexcess saturated sodium bicarbonate solution, added with ethyl acetate(100 mL), and filtered through celite, and the organic phase was driedover anhydrous sodium sulfate. The organic phase was then removed of thesolvent under reduced pressure, and then purified by columnchromatography to obtain 4a as a white solid (2.5 g, yield=90%).

White solid. ¹H NMR (400 MHz, CDCl₃) δ 4.58-4.62 (m, 2H, CH₂), 4.69-4.72(m, 1H, CH₂), 5.08-5.12 (m, 1H, CH₂), 6.32-6.34 (m, 1H, Ar), 6.51-6.52(m, 1H, Ar), 6.72-6.74 (m, 1H, Ar), 6.81-6.85 (m, 1H, Ar), 6.88-6.91 (m,2H, Ar), 6.99-7.05 (m, 3H, Ar), 7.10-7.13 (m, 2H, Ar), 7.14-7.22 (m, 4H,Ar). ¹³C {1H} NMR (126 MHz, CDCl₃) δ 162.6, 160.3, 145.4, 136.6, 134.5(m), 133.5 (m), 132.0, 131.3, 130.1, 128.8 (m), 127.8, 122.6, 112.3,110.9, 109.5, 84.5, 83.0, 56.3. ³¹P {1H} NMR (202 MHz, CDCl₃) δ −22.32(s). HRMS (ESI) calcd. for C₁₈H₂₁O₅F₃PS [M+H]⁺: 557.0799, Found:557.0794, [α]²⁰ _(D)=+56.0 (c=0.5, acetone).

Example 4 Synthesis of(R)-(4′-(diphenylphosphine)-2H,2′H-3,3′-spirobi[benzofuran]-4-diphenylphosphineoxide 5a

Under a N₂ atmosphere, 4a (2.78 g, 5 mmol), dppb (107 mg, 0.025 mmol),Ph₂POH (1.94 g, 7.5 mmol), Pd(PAc)₂ (56 mg, 0.0025 mmol), and DIPEA (3.2mL, 20 mmol) were added to a reaction flask, and finally DMSO (20 mL)containing no water and oxygen was added. The reaction was continued at100° C. for 6 h. After cooling to room temperature, water was added toquench the reaction, and the reaction system was extracted with ethylacetate. The organic phase was dried over anhydrous sodium sulfate,removed of the solvent under reduced pressure, and simply purified bycolumn chromatography to obtain the product 5a (2.66 g, yield=87%).

White solid. ¹H NMR (500 MHz, CDCl₃) δ 4.38 (d, J=9.5 Hz, 1H, CH₂), 4.43(d, J=9.0 Hz, 1H, CH₂), 4.46 (d, J=9.5 Hz, 1H, CH₂), 5.19 (d, J=9.0 Hz,1H, CH₂), 6.56-6.59 (m, 1H, Ar), 6.74-6.84 (m, 4H, Ar), 7.01-7.03 (m,1H, Ar), 7.07-7.12 (m, 3H, Ar), 7.17-7.30 (m, 6H, Ar), 7.32-7.36 (m, 5H,Ar), 7.38-7.43 (m, 3H, Ar), 7.48-7.55 (m, 3H, Ar). ¹³C {1H} NMR (126MHz, CDCl₃) δ 162.9, 160.4, 138.1, 137.9, 137.4, 134.9, 134.4 (m), 134.1(m), 133.3 (m), 132.5, 132.1, 131.7 (m), 129.8, 128.9 (m), 128.4 (m),128.1 (m), 126.7 (m), 113.4, 110.2, 85.2, 84.0, 58.2 (m). ³¹P {1H} NMR(162 MHz, CDCl₃) δ 29.41 (s), −20.96 (s). HRMS (ESI) calcd. forC₃₉H₃₁O₃P₂ [M+H]⁺: 609.1748, Found: 609.1743, [α]²⁰ _(D)=+224.0 (c=0.5,acetone).

Example 5 Synthesis of(R)-4,4′-bis(diphenylphosphine)-2H,2′H-3,3′-spirobi[benzfuran] 6a

In a 100 mL sealed tube, 3a (1.216 g, 2 mmol), DIPEA (3.3 mL, 20 mmol),toluene (10 mL), and trichlorosilane (1.0 mL, 10 mmol) were added. Thereaction was stirred overnight at 120° C. The reaction system wasquenched with excess saturated sodium bicarbonate solution, added withethyl acetate (100 mL), and filtered through celite, and the organicphase was dried over anhydrous sodium sulfate. The organic phase wasthen removed of the solvent under reduced pressure, and then purified bycolumn chromatography to obtain 6a as a white solid (1.15 g, yield=96%).

White solid. ¹H NMR (500 MHz, CDCl₃) δ 4.38 (d, J=9.5 Hz, 2H, CH₂), 4.49(d, J=9.5 Hz, 2H, CH₂), 6.67-6.68 (m, 2H, Ar), 6.85-6.86 (m, 2H, Ar),6.92 (s, 4H, Ar), 7.01-7.03 (m, 1H, Ar), 7.11-7.23 (m, 12H, Ar),7.29-7.30 (m, 6H, Ar). ¹³C {1H} NMR (126 MHz, CDCl₃) δ 160.8 (t, J=7.5Hz), 137.1, 136.8, 135.0, 134.1, 133.4, 129.5, 128.7 128.4, 128.0,127.3, 110.4, 83.6, 58.0 (m). ³¹P {1H} NMR (162 MHz, CDCl₃) δ −20.99(s). HRMS (ESI) calcd. for C₃₉H₃₁O₂P₂ [M+H]⁺: 593.1799, Found: 593.1782,[α]²⁰ _(D)=+246 (c=0.5, acetone).

Example 6 Synthesis of (R)-4′-(di-p-methylphenylphosphineoxide)-2H,2′H-3,3′-spirobi benzofuran-4-trifluoromethanesulfonate 3b

Under a N₂ atmosphere, 2 (2.6 g, 5 mmol), dppb (107 mg, 0.025 mmol),Ar₂POH (1.73 g, 7.5 mmol), Pd(PAc)₂ (56 mg, 0.025 mmol), and DIPEA (3.2mL, 20 mmol) were added to a reaction flask, and finally DMSO (30 mL)containing no water and oxygen was added. The reaction was continued at100° C. for 6 h. After cooling to room temperature, water was added toquench the reaction, and the reaction system was extracted with ethylacetate. The organic phase was dried over anhydrous sodium sulfate,removed of the solvent under reduced pressure, and simply purified bycolumn chromatography to obtain the product 3b (2.60 g, yield=87%).

White solid. ¹H NMR (500 MHz, CDCl₃) δ 2.36 (s, 3H, CH₃), 2.38 (s, 3H,CH₃), 4.60-4.62 (m, 1H, CH₂), 4.70-4.74 (m, 2H, CH₂), 5.69 (d, =8.5 Hz,1H, CH₂), 6.17 (d, J⁼8.0 Hz, 1H, Ar), 6.66-6.70 (m, 1H, Ar), 6.80-6.81(m, 1H, Ar), 7.03-7.07 (m, 2H, Ar), 7.10-7.16 (m, 4H, Ar), 7.18-7.21 (m,3H, Ar), 7.36-7.40 (m, 2H, Ar). ¹³C {1H} NMR (126 MHz, CDCl₃) δ 163.8,161.9, 144.7, 142.0 (m), 131.9 (m), 131.5 (m), 131.2 (m), 130.7 (m),130.2, 130.0, 129.3, 129.0 (m), 128.1, 126.9, 123.5, 121.8, 119.8,116.6, 113.8, 111.7, 109.3, 85.6, 83.6, 56.5, 21.5. ³¹P {1H} NMR (202MHz, CDCl₃) δ 29.86 (s). HRMS (ESI) calcd. for C₃₀H₂₅O₆F₃PS [M+H]⁺:601.1062, Found: 601.1056, [α]²⁰ _(D)=+108.4 (c=0.5, acetone).

Example 7 Synthesis of(R)-4′-(di-p-methylphenylphosphine)-2H,2′H-3,3′-spirobi[benzofuran]-4-trifluoromethanesulfonate4b

In a 100 mL sealed tube, 3b (3.00 g, 5 mmol), DIPEA (3.2 mL, 20 mmol),toluene (20 mL), and trichlorosilane (2.0 mL, 20 mmol) were added. Thereaction was stirred overnight at 120° C. The reaction system wasquenched with excess saturated sodium bicarbonate solution, added withethyl acetate (100 mL), and filtered through celite, and the organicphase was dried over anhydrous sodium sulfate. The organic phase wasthen removed of the solvent under reduced pressure, and then purified bycolumn chromatography to obtain 4b as a white solid (2.70 g, yield=92%).

White solid. ¹H NMR (400 MHz, CDCl₃) δ 4.58-4.62 (m, 2H, CH₂), 4.69-4.72(m, 1H, CH₂), 5.08-5.12 (m, 1H, CH₂), 6.43 (d, J=9.0 Hz, 1H, Ar),6.51-6.52 (m, 1H, Ar), 6.72-6.74 (m, 1H, Ar), 6.81-6.85 (m, 1H, Ar),6.88-6.91 (m, 2H, Ar), 6.99-7.05 (m, 3H, Ar), 7.10-7.13 (m, 2H, Ar),7.14-7.22 (m, 4H, Ar). ¹³C {1H} NMR (101 MHz, CDCl₃) δ 162.7, 160.2,153.6, 145.5, 138.6, 133.7, 133.5, 131.1, 129.9, 129.3, 129.0, 127.6,122.6, 112.3, 110.7, 109.4, 84.3, 82.9, 56.3, 26.9, 21.2. ³¹P {1H} NMR(202 MHz, CDCl₃) δ −22.32 (s). HRMS (ESI) calcd. for C₃₀H₂₅O₅F₃PS[M+H]⁺: 585.1112, Found: 585.1107, [α]²⁰ _(D)=+111.4 (c=0.5, acetone).

Example 8 Synthesis of(R)-(4′-(di-p-methylphenylphosphine)-2H,2′H-3,3′-spirobi[benzofuran]-4-diphenylphosphineoxide 5b

Under a N₂ atmosphere, 4b (0.584 g, 2 mmol), dppb (43 mg, 0.1 mmol),Ph₂POH (0.69 g, 3 mmol), Pd(PAc)₂ (22.4 mg, 0.1 mmol), and DIPEA (0.50mL, 4 mmol) were added to a reaction flask, and finally DMSO (20 mL)containing no water and oxygen was added. The reaction was continued at100° C. for 6 h. After cooling to room temperature, water was added toquench the reaction, and the reaction system was extracted with ethylacetate. The organic phase was dried over anhydrous sodium sulfate,removed of the solvent under reduced pressure, and simply purified bycolumn chromatography to obtain the product 5b (1.12 g, yield=85%).

White solid. ¹H NMR (500 MHz, CDCl₃) δ 2.27 (s, 3H, CH₃), 2.31 (s, 6H,CH₃), 2.35 (s, 3H, CH₃) 4.36 (d, J=9.0 Hz, 1H, CH₂), 4.44 (t, J=9.5 Hz,2H, CH₂), 5.25 (d, J=9.0 Hz, 1H, CH₂), 6.56-6.58 (m, 1H, Ar), 6.67-6.70(m, 2H, Ar), 6.74-6.78 (m, 1H, Ar), 6.79-6.80 (m, 1H, Ar), 6.89-6.91 (m,2H, Ar), 6.97-7.00 (m, 3H, Ar), 7.04-7.12 (m, 5H, Ar), 7.18-7.26 (m, 5H,Ar), 7.37-7.42 (m, 2H, Ar). ¹³C {1H} NMR (126 MHz, CDCl₃) δ 171.0,162.8, 160.2, 141.7, 141.5, 138.5, 137.8, 137.6, 137.3, 134.0 (m),133.2, 132.1, 131.7, 131.2, 130.0, 129.2 (m), 128.7 (m), 126.4, 113.0,109.9, 85.0, 84.0, 60.3, 58.1 (m), 21.5, 21.2. ³¹P {1H} NMR (202 MHz,CDCl₃) δ 29.37 (s), −22.71 (s). HRMS (ESI) calcd. for C₄₃H₃₉O₃P₂ [M+H]⁺:665.2374, Found: 665.2369, [α]²⁰ _(D)=+211.2 (c=0.5, acetone).

Example 9 Synthesis of(R)-4,4′-bis(di-p-methylphenylphosphine)-2H,2′H-3,3′-spirobi[benzofuran]6b

In a 100 mL sealed tube, 5b (0.664 g, 1 mmol), DIPEA (3.3 mL, 20 mmol),toluene (10 mL), and trichlorosilane (1.0 mL, 10 mmol) were added. Thereaction was stirred overnight at 120° C. The reaction system wasquenched with excess saturated sodium bicarbonate solution, added withethyl acetate (100 mL), and filtered through celite, and the organicphase was dried over anhydrous sodium sulfate. The organic phase wasthen removed of the solvent under reduced pressure, and then purified bycolumn chromatography to obtain 6b as a white solid (0.62 g, yield=95%).

White solid. ¹H NMR (500 MHz, CDCl₃) δ 2.29 (s, 6H, CH₃), 2.33 (s, 6H,CH₃), 4.35 (d, J=9.5 Hz, 2H, CH₂), 4.44 (d, J=9.0 Hz, 2H, CH₂),6.66-6.68 (m, 2H, Ar), 6.81-6.84 (m, 6H, Ar), 6.93-6.95 (m, 4H, Ar),7.10 (s, 8H, Ar), 7.14-7.17 (m, 2H, Ar). ¹³C {1H} NMR (126 MHz, CDCl₃) δ160.8 (m), 138.6, 137.7, 135.8, 134.8 (m), 134.2 (m), 133.5 (m), 129.2(m), 128.8 (m), 110.1, 83.6 (m), 58.0 (m), 21.3. ³¹P {1H} NMR (202 MHz,CDCl₃) δ −22.82 (s). HRMS (ESI) calcd. for C₄₃H₃₉O₂P₂ [M+H]⁺: 649.2425,Found: 649.2420, [α]²⁰ _(D)=+231.2 (c=0.5, acetone).

Example 10 Synthesis of (R)-4′-(di-p-methoxyphenylphosphineoxide)-2H,2′H-3,3′-spirobi[benzofuran]-4-trifluoromethanesulfonate 3c

Under a N₂ atmosphere, 2 (5.2 g, 10 mmol), dppb (213 mg, 0.05 mmol),Ar₂POH (3.93 g, 15 mmol), Pd(PAc)₂ (112 mg, 0.05 mmol), and DIPEA (6.5mL, 40 mmol) were added to a reaction flask, and finally DMSO (50 mL)containing no water and oxygen was added. The reaction was continued at100° C. for 6 h. After cooling to room temperature, water was added toquench the reaction, and the reaction system was extracted with ethylacetate. The organic phase was dried over anhydrous sodium sulfate,removed of the solvent under reduced pressure, and simply purified bycolumn chromatography to obtain the product 3c (5.78 g, yield=91%).

White solid. ¹H NMR (500 MHz, CDCl₃) δ 3.81 (s, 3H, CH₃), 3.84 (s, 31,CH₃), 4.62 (d, J=9.5 Hz, 1H, CH₂), 4.70-4.75 (m, 2H, CH₂), 5.71 (d,J=8.5 Hz, 1H, CH₂), 6.23 (d, J=8.5 Hz, 1H, CH₂), 6.65-6.70 (m, 1H, Ar),6.80-6.82 (m, 3H, Ar), 6.88-6.91 (m, 2H, Ar), 7.03-7.07 (m, 2H, Ar),7.16-7.27 (m, 3H, Ar), 7.39-7.43 (m, 2H, Ar). ¹³C {1H} NMR (126 MHz,CDCl₃) δ 163.8, 162.2 (m), 144.7, 133.7, 133.0, 131.4 (m), 130.3 (m),129.3, 126.9, 125.9, 125.0, 122.8, 121.7 (m), 119.1, 116.6, 113.8 (m),111.5, 109.2, 85.6, 83.6, 56.5, 55.2. ³¹P {1H}NMR (202 MHz, CDCl₃) δ29.39 (s). HRMS (ESI) calcd. for C₃₀H₂₅O₈F₃PS [M+H]⁺: 633.0960, Found:633.0954, [α]²⁰ _(D)=+62.4 (c=0.5, acetone).

Example 11 Synthesis of(R)-4′-(di-p-methoxyphenylphosphine)-2H,2′H-3,3′-spirobi[benzofuran]-4-trifluoromethanesulfonate4c

In a 100 mL sealed tube, 3c (2.86 g, 5 mmol), DIPEA (6.6 mL, 40 mmol),(20 mL), and trichlorosilane (2.0 mL, 20 mmol) were added. The reactionwas stirred overnight at 120° C. The reaction system was quenched withexcess saturated sodium bicarbonate solution, added with ethyl acetate(100 mL), and filtered through celite, and the organic phase was driedover anhydrous sodium sulfate. The organic phase was then removed of thesolvent under reduced pressure, and then purified by columnchromatography to obtain 4c as a white solid (2.81 g, yield=91%).

White solid. ¹H NMR (400 MHz, CDCl₃) δ 4.58-4.62 (m, 2H, CH₂), 4.69-4.72(m, 1H, CH₂), 5.08-5.12 (m, 1H, CH₂), 6.43 (d, J=9.0 Hz, 1H, Ar),6.51-6.52 (m, 1H, Ar), 6.72-6.74 (m, 1H, Ar), 6.81-6.85 (m, 1H, Ar),6.88-6.91 (m, 2H, Ar), 6.99-7.05 (m, 3H, Ar), 7.10-7.13 (m, 2H, Ar),7.14-7.22 (m, 4H, Ar). ¹³C {1H} NMR (101 MHz, CDCl₃) δ 162.7, 160.2,153.6, 145.5, 138.6, 133.7, 133.5, 131.1, 129.9, 129.3, 129.0, 127.6,122.6, 112.3, 110.7, 109.4, 84.3, 82.9, 56.3, 26.9, 21.2. ³¹P {1H} NMR(202 MHz, CDCl₃) δ −22.32 (s). HRMS (ESI) calcd. for C₃₀H₂₅O₅F₃PS[M+H]⁺: 585.1112, Found: 585.1107, [α]²⁰ _(D)=+111.4 (c=0.5, acetone).

Example 12 Synthesis of(R)-(4′-(di-p-methoxyphenylphosphine)-2H,2′H-3,3′-spirobi[benzofuran]-4-diphenylphosphineoxide 5c

Under a N₂ atmosphere, 4c (1.232 g, 2 mmol), dppb (43 mg, 0.1 mmol),Ph₂POH (0.79 g, 3 mmol), Pd(PAc)₂ (22.4 mg, 0.1 mmol), and DIPEA (1.6mL, 5 mmol) were added to a reaction flask, and finally DMSO (20 mL)containing no water and oxygen was added. The reaction was continued at100° C. for 6 h. After cooling to room temperature, water was added toquench the reaction, and the reaction system was extracted with ethylacetate. The organic phase was dried over anhydrous sodium sulfate,removed of the solvent under reduced pressure, and simply purified bycolumn chromatography to obtain the product 5c (1.27 g, yield=87%).

White solid. ¹H NMR (500 MHz, CDCl₃) δ 3.73 (s, 3H, CH₃), 3.74 (s, 3H,CH₃), 3.77 (s, 6H, CH₃), 3.80 (s, 3H, CH₃) 4.37 (d, J=9.0 Hz, 1H, CH₂),4.45-4.47 (m, 2H, CH₂), 5.28 (d, J=9.0 Hz, 1H, CH₂), 6.55-6.57 (m, 1H,Ar), 6.64-6.71 (m, 61, Ar), 6.75-6.83 (m, 4H, Ar), 6.89-6.91 (m, 2H,Ar), 6.98-7.00 (m, 1H, Ar), 7.06-7.11 (m, 1H, Ar), 7.13-7.14 (m, 2H,Ar), 7.20-7.26 (m, 3H, Ar), 7.42-7.45 (m, 2H, Ar). ¹³C {1H} NMR (126MHz, CDCl₃) δ 171.0, 162.8 (m), 161.9 (m), 160.3 (m), 137.5, 135.4,134.8, 134.0 (m), 133.5, 130.6, 129.9, 128.5 (m), 128.1, 126.6 (m),126.0 (m), 124.7, 123.8, 113.9 (m), 112.9, 109.8, 85.0, 84.2, 60.3, 58.1(m), 55.0 (m). ³¹P {1H} NMR (202 MHz, CDCl₃) δ 28.75 (s), −24.27 (s).HRMS (ESI) calcd. for C₄₃H₃₉O₇P₂ [M+H]⁺: 729.2171, Found: 729.2166,[α]²⁰ _(D)=+173.2 (c=0.5, acetone).

Example 13 Synthesis of(R)-4,4′-bis(di-p-methylphenylphosphine)-2H,2′H-3,3′-spirobi[benzofuran]6c

In a 100 mL sealed tube, 5c (0.728 g, 1 mmol), DIPEA (1.65 mL, 10 mmol),toluene (10 mL), and trichlorosilane (1.0 mL, 10 mmol) were added. Thereaction was stirred overnight at 120° C. The reaction system wasquenched with excess saturated sodium bicarbonate solution, added withethyl acetate (100 mL), and filtered through celite, and the organicphase was dried over anhydrous sodium sulfate. The organic phase wasthen removed of the solvent under reduced pressure, and then purified bycolumn chromatography to obtain 6c as a white solid (0.64 g, yield=90%).

White solid. ¹H NMR (500 MHz, CDCl₃) δ 3.75 (s, 6H, CH₃), 3.79 (s, 6H,CH₃), 4.36 (d, J=9.0 Hz, 2H, CH₂), 4.46 (d, J=9.5 Hz, 2H, CH₂),6.64-6.70 (m, 6H, Ar), 6.82-6.85 (m, 10H, Ar), 7.12-7.18 (m, 6H, Ar).¹³C {1H} NMR (126 MHz, CDCl₃) δ 160.8 (m), 160.1 (m), 136.2 (m), 135.5(m), 134.5 (m), 129.3, 128.3 (m), 126.8, 114.0 (m), 110.0, 83.6 (m),57.9 (m), 55.1 (m). ³¹P {1H} NMR (202 MHz, CDCl₃) δ −24.20 (s). HRMS(ESI) calcd. for C₄₃H₃₉O₂P₂ [M+H]⁺: 649.2425, Found: 649.2420, [α]²⁰_(D)=+133.6 (c=0.5, acetone).

Example 14 Synthesis of (R)-4′-bis(3,5-dimethylphenyl)phosphineoxide)-2H,2′H-3,3′-spirobi[benzofuran]-4-trifluoromethanesulfonate 3d

Under a N₂ atmosphere, 2 (5.20 g, 10 mmol), dppb (213 mg, 0.05 mmol),Ar₂POH (3.87 g, 15 mmol), Pd(PAc)₂ (112 mg, 0.05 mmol), and DIPEA (6.5mL, 40 mmol) were added to a reaction flask, and finally DMSO (50 mL)containing no water and oxygen was added. The reaction was continued at100° C. for 6 h. After cooling to room temperature, water was added toquench the reaction, and the reaction system was extracted with ethylacetate. The organic phase was dried over anhydrous sodium sulfate,removed of the solvent under reduced pressure, and simply purified bycolumn chromatography to obtain the product 3d (5.15 g, yield=82%).

White solid. ¹H NMR (500 MHz, CDCl₃) δ 2.15 (s, 6H, CH₃), 2.17 (s, 6H,CH₃), 4.54 (d, J=9.5 Hz, 1H, CH₂), 4.62-4.64 (m, 2H, CH₂), 5.69 (d,J=8.5 Hz, 1H, CH₂), 6.07 (d, J=8.0 Hz, 1H, Ar), 6.63-6.67 (m, 1H, Ar),6.72-6.78 (m, 3H, Ar), 6.93-6.98 (m, 2H, Ar), 7.00-7.05 (m, 4H, Ar),7.12-7.18 (m, 1H, Ar). ¹³C {1H} NMR (126 MHz, CDCl₃) δ 163.9, 161.7,144.7, 137.8 (m), 133.9, 133.3 (m), 131.5, 130.7, 130.0 (m), 129.4 (m),128.7, 126.9, 121.6, 119.1, 116.5, 113.6, 111.3, 109.1, 85.7, 83.6,56.3, 21.2. ³¹P {1H} NMR (202 MHz, CDCl₃) δ 29.59 (s). HRMS (ESI) calcd.for C₃₂H₂₉O₆F₃PS [M+H]⁺: 629.1375, Found: 629.1369, [α]²⁰ _(D)=+196.4(c=0.5, acetone).

Example 15 Synthesis of(R)-4′-(3,5-dimethylphenylphosphine)-2H,2′H-33′-spirobi[benzofuran]-4-trifluoromethanesulfonate4d

In a 100 mL sealed tube, 3d (3.14 g, 5 mmol), DIPEA (6.6 mL, 40 mmol),(20 mL), and trichlorosilane (2.0 mL, 20 mmol) were added. The reactionwas stirred overnight at 120° C. The reaction system was quenched withexcess saturated sodium bicarbonate solution, added with ethyl acetate(100 mL), and filtered through celite, and the organic phase was driedover anhydrous sodium sulfate. The organic phase was then removed of thesolvent under reduced pressure, and then purified by columnchromatography to obtain 4d as a white solid (2.88 g, yield=94%).

White solid. ¹H NMR (400 MHz, CDCl₃) δ 2.16 (s, 6H, CH₃), 2.19 (s, 6H,CH₃), 4.44 (d, J=9.0 Hz, 1H, CH₂), 4.63-4.67 (m, 2H, CH₂), 5.15-5.18 (m,1H, CH₂), 6.36-6.40 (m, 1H, Ar), 6.51-6.53 (m, 3H, Ar), 6.65-6.68 (m,1H, Ar), 6.73-6.79 (m, 3H, Ar), 6.83-6.87 (m, 3H, Ar), 6.99-7.01 (m, 1H,Ar), 7.11-7.15 (m, 1H, Ar). ¹³C {1H} NMR (101 MHz, CDCl₃) δ 162.6,160.2, 145.3, 137.7 (m), 136.3, 135.2, 134.0, 131.8 (m), 130.5 (m),129.9, 127.7, 122.8, 119.3, 116.7, 112.1, 110.6, 109.4, 84.4, 83.0,56.2, 21.3. ³¹P {1H} NMR (162 MHz, CDCl₃) δ −21.56 (s). HRMS (ESI)calcd. for C₃₂H₂₉O₅F₃PS [M+H]⁺: 613.1425, Found: 613.1420, [α]²⁰_(D)=+60.0 (c=0.5, acetone).

Example 16 Synthesis of (R)-(4′-(3,5-dimethylphenylphosphine)-2H,2′H-3,3′-spirobi[benzofuran]-4-diphenylphosphine oxide 5b

Under a N₂ atmosphere, 4d (1.22 g, 2 mmol), dppb (107 mg, 0.1 mmol),Ph₂POH (0.77 g, 3 mmol), Pd(PAc)₂ (22.4 mg, 0.1 mmol), and DIPEA (0.8mL, 5 mmol) were added to a reaction flask, and finally DMSO (10 mL)containing no water and oxygen was added. The reaction was continued at100° C. for 6 h. After cooling to room temperature, water was added toquench the reaction, and the reaction system was extracted with ethylacetate. The organic phase was dried over anhydrous sodium sulfate,removed of the solvent under reduced pressure, and simply purified bycolumn chromatography to obtain the product 5d (1.22 g, yield=86%).

White solid. ¹H NMR (500 MHz, CDCl₃) δ 2.04 (s, 6H, CH₃), 2.06 (s, 6H,CH₃), 2.24 (s, 6H, CH₃), 2.29 (s, 6H, CH₃), 4.14 (d, J=9.5 Hz, 1H, CH₂),4.41 (d, J=9.5 Hz, 2H, CH₂), 5.15 (d, J=8.5 Hz, 1H, CH₂), 6.49 (d, J=7.5Hz, 1H, Ar), 6.70-6.73 (m, 1H, Ar), 6.75-6.78 (m, 2H, Ar), 6.86-6.90 (m,3H, Ar), 6.95-6.98 (m, 3H, Ar), 7.03-7.06 (m, 2H, Ar), 7.07 (s, 1H, Ar),7.09 (s, 1H, Ar), 7.19 (s, 1H, Ar), 7.21 (s, 1H, Ar), 7.24-7.25 (m, 1H,Ar). ¹³C {1H} NMR (126 MHz, CDCl₃) δ 162.8 (m), 159.8 (m), 137.7 (m),136.8 (m), 135.0, 134.2, 134.0.133.2 (m), 132.8, 132.4 (m), 130.8 (m),130.0 (m), 129.4 (m), 128.5 (m), 126.7, 126.4, 112.9, 109.9, 84.1, 83.3,58.3 (m), 21.3 (m). ³¹P {1H} NMR (202 MHz, CDCl₃) δ −19.53 (s), 29.83(s). HRMS (ESI) calcd. for C₄₇H₄₇O₃P₂ [M+H]⁺: 721.3000, Found: 721.2995,[α]²⁰ _(D)=+137.2 (c=0.5, acetone).

Example 17 Synthesis of(R)-4,4′-bis(3,5-diphenylphosphine)-2H,2′H-3,3′-spirobi[benzofuran] 6d

In a 100 mL sealed tube, 5d (0.72 g, 1 mmol), DIPEA (3.3 mL, 20 mmol),toluene (10 mL), and trichlorosilane (1.0 mL, 10 mmol) were added. Thereaction was stirred overnight at 120° C. The reaction system wasquenched with excess saturated sodium bicarbonate solution, added withethyl acetate (100 mL), and filtered through celite, and the organicphase was dried over anhydrous sodium sulfate. The organic phase wasthen removed of the solvent under reduced pressure, and then purified bycolumn chromatography to obtain 6d as a white solid (0.65 g, yield=93%).

White solid. ¹H NMR (500 MHz, CDCl₃) δ 2.07 (s, 6H, CH₃), 2.09 (s, 6H,CH₃), 2.24 (s, 6H, CH₃), 2.26 (s, 6H, CH₃), 4.19-4.20 (m, 2H, CH₂),4.31-4.34 (m, 2H, CH₂), 6.65-6.66 (m, 4H, Ar), 6.81-6.84 (m, 6H, Ar),6.85-6.88 (m, 4H, Ar), 6.95-6.96 (m, 2H, Ar), 7.18-7.22 (m, 2H, Ar). ¹³C{1H} NMR (126 MHz, CDCl₃) δ 160.9 (m), 137.7 (m), 137.2 (m), 136.1,133.8 (m), 132.3 (m), 131.0 (m), 129.6 (m), 127.1, 110.1, 82.9, 58.3(m), 21.3 (m). ³¹P {1H} NMR (202 MHz, CDCl₃) δ −19.92 (s). HRMS (ESI)calcd. for C₄₇H₄₇O₂P₂ [M+H]⁺: 705.3051, Found: 705.3046, [α]²⁰n=+138.0(c=0.5, acetone).

Example 18 Synthesis of (R)-4′-(3,5-di-t-butylphenylphosphineoxide)-2H,2′H-3,3′-spirobi[benzofuran]-4-trifluoromethanesulfonate 3e

Under a N₂ atmosphere, 2 (5.2 g, 10 mmol), dppb (213 mg, 0.05 mmol),Ar₂POH (6.39 g, 15 mmol), Pd(PAc)₂ (112 mg, 0.05 mmol), and DIPEA (6.5mL, 40 mmol) were added to a reaction flask, and finally DMSO (50 mL)containing no water and oxygen was added. The reaction was continued at100° C. for 6 h. After cooling to room temperature, water was added toquench the reaction, and the reaction system was extracted with ethylacetate. The organic phase was dried over anhydrous sodium sulfate,removed of the solvent under reduced pressure, and simply purified bycolumn chromatography to obtain the product 3e (7.43 g, yield=93%).

White solid. ¹H NMR (500 MHz, CDCl₃) δ 1.18 (s, 9H, CH₃), 1.19 (s, 9H,CH₃), 1.20 (s, 9H, CH₃), 1.21 (s, 9H, CH₃), 4.54-4.56 (m, 1H, CH₂),4.62-4.64 (m, 1H, CH₂), 4.80-4.82 (m, 2H, CH₂), 6.63-6.68 (m, 2H, Ar),6.82-6.88 (m, 6H, Ar), 6.90-6.94 (m, 2H, Ar), 7.15-7.21 (m, 1H, Ar),7.26-7.34 (m, 1H, Ar). ¹³C {1H} NMR (126 MHz, CDCl₃) δ 162.9, 160.1,150.5, 150.2, 145.7, 136.0 (m), 135.5, 134.4, 131.2, 129.6, 128.4,127.5, 122.4 (m), 112.5, 110.5, 109.6, 83.5, 82.3, 56.4 (m), 34.8 (m),31.3 (m). ³¹P {1H} NMR (202 MHz, CDCl₃) δ −19.74 (s). HRMS (ESI) calcd.for C₄₄H₅₃O₆F₃PS [M+H]⁺: 797.3253, Found: 797.3247, [α]²⁰ _(D)=+109.6(c=0.5, acetone).

Example 19 Synthesis of(R)-4′-(3,5-di-t-butylphenylphosphine)-2H,2′H-3,3′-spirobi[benzofuran]-4-trifluoromethanesulfonate4e

In a 100 mL sealed tube, 3e (3.98 g, 5 mmol), DIPEA (6.6 mL, 40 mmol),(20 mL), and trichlorosilane (2.0 mL, 20 mmol) were added. The reactionwas stirred overnight at 120° C. The reaction system was quenched withexcess saturated sodium bicarbonate solution, added with ethyl acetate(100 mL), and filtered through celite, and the organic phase was driedover anhydrous sodium sulfate. The organic phase was then removed of thesolvent under reduced pressure, and then purified by columnchromatography to obtain 4e as a white solid (3.51 g, yield=90%).

White solid. ¹H NMR (500 MHz, CDCl₃) δ 1.17 (s, 9H, CH₃), 1.19 (s, 9H,CH₃), 1.20 (s, 9H, CH₃), 1.21 (s, 9H, CH₃), 4.52-4.55 (m, 1H, CH₂),4.60-4.63 (m, 1H, CH₂), 4.77-4.82 (m, 2H, CH₂), 6.61-6.69 (m, 2H, Ar),6.80-6.94 (m, 6H, Ar), 7.14-7.22 (m, 2H, Ar), 7.28-7.34 (m, 2H, Ar). ¹³C{1H} NMR (126 MHz, CDCl₃) δ 162.9, 160.1 (m), 150.5 (m), 145.8, 136.1(m), 135.5 (m), 134.4, 131.9 (m), 131.2, 129.6, 128.4 (m), 127.5, 122.4(m), 116.9, 112.6, 110.6, 109.6, 83.5, 82.4, 56.4 (m), 34.8 (m), 31.3(m). ³¹P {1H} NMR (202 MHz, CDCl₃) δ −19.73 (s). HRMS (ESI) calcd. forC₃₂H₂₉O₅F₃PS [M+H]⁺: 781.3303, Found: 781.3298, [α]²⁰ _(D)=+78.8 (c=0.5,acetone).

Example 20 Synthesis of (R)-(4′-(3,5-di-t-butylphenylphosphine)-2H,2′H-3,3′-spirobi[benzofuran]-4-di phenyl phosphineoxide 5e

Under a N₂ atmosphere, 4e (1.56 g, 2 mmol), dppb (43 mg, 0.1 mmol),Ph₂POH (1.28 g, 3 mmol), Pd(PAc)₂ (22.4 mg, 0.1 mmol), and DIPEA (1.6mL, 10 mmol) were added to a reaction flask, and finally DMSO (10 mL)containing no water and oxygen was added. The reaction was continued at100° C. for 6 h. After cooling to room temperature, water was added toquench the reaction, and the reaction system was extracted with ethylacetate. The organic phase was dried over anhydrous sodium sulfate,removed of the solvent under reduced pressure, and simply purified bycolumn chromatography to obtain the product 5e (1.85 g, yield=92%).

White solid. ¹H NMR (500 MHz, CDCl₃) δ 1.95 (s, 18H, CH₃), 1.02 (s, 18H,CH₃), 1.27 (s, 18H, CH₃), 1.30 (s, 18H, CH₃), 3.78 (d, J=8.8 Hz, 1H,CH₂), 4.36 (d, J=9.6 Hz, 1H, CH₂), 4.45 (d, J=8.4 Hz, 1H, CH₂), 4.91 (d,J=8.4 Hz, 1H, CH₂), 6.67 (d, J=6.8 Hz, 2H, Ar), 6.76-6.78 (m, 1H, Ar),6.86-6.90 (m, 2H, Ar), 6.97-7.01 (m, 1H, Ar), 7.06-7.10 (m, 2H, Ar),7.16-7.20 (m, 1H, Ar), 7.22-7.24 (m, 2H, Ar), 7.39 (s, 2H, Ar), 7.41 (s,2H, Ar), 7.49 (s, 2H, Ar), 7.61 (d, J=8.0 Hz, 2H, Ar), 7.65 (d, J=9.6Hz, 2H, Ar). ¹³C {1H} NMR (126 MHz, CDCl₃) δ 162.3, 159.0, 150.4 (m),149.5 (m), 137.7, 137.3 (m), 135.5 (m), 134.7, 133.9 (m), 132.9, 132.4(m), 129.6 (m), 128.0 (m), 127.5, 126.5 (m), 122.9, 120.7, 112.2, 109.9,81.4, 81.3, 59.1, 34.8 (m), 31.2 (m). ³¹P {1H} NMR (202 MHz, CDCl₃) δ30.86 (s), −16.07 (s). HRMS (ESI) calcd. for C₇₁H₉₅O₃P₂ [M+H]⁺:1057.6756, Found: 1057.6751, [α]²⁰ _(D)=+152.4 (c=0.5, acetone).

Example 21 Synthesis of (R)-4,4′-bis(3,5-di-butylphenylphosphine)-2H,2′H-3,3′-spirobi[benzofuran] 6e

In a 100 mL sealed tube, 5e (1.01 g, 1 mmol), DIPEA (1.65 mL, 10 mmol),toluene (10 mL), and trichlorosilane (1.0 mL, 10 mmol) were added. Thereaction was stirred overnight at 120° C. The reaction system wasquenched with excess saturated sodium bicarbonate solution, added withethyl acetate (100 mL), and filtered through celite, and the organicphase was dried over anhydrous sodium sulfate. The organic phase wasthen removed of the solvent under reduced pressure, and then purified bycolumn chromatography to obtain 6e as a white solid (0.82 g, yield=79%).

White solid. ¹H NMR (500 MHz, CDCl₃) δ 0.99 (s, 36H, CH₃), 1.25 (s, 36H,CH₃), 3.85 (d, J=9.0 Hz, 2H, CH₂), 4.25 (d, J=8.5 Hz, 2H, CH₂), 6.80 (d,J=8.0 Hz, 2H, Ar), 6.91-6.93 (m, 2H, Ar), 7.01-7.02 (m, 4H, Ar),7.09-7.10 (m, 2H, Ar), 7.15-7.18 (m, 2H, Ar), 7.25-7.36 (m, 4H, Ar),7.37 (s, 2H, Ar). ¹³C {1H} NMR (126 MHz, CDCl₃) δ 160.5 (m), 150.4 (m),149.2 (m), 139.0, 137.4, 135.5 (m), 131.4 (m), 129.6 (m), 126.9 (m),123.0, 120.9, 110.0, 80.4, 59.1 (m), 34.8 (m), 31.4 (m). ³¹P {1H} NMR(202 MHz, CDCl₃) δ −15.41 (s). HRMS (ESI) calcd. for C₇₁H₉₅O₂P₂ [M+H]⁺:1041.6807, Found: 1041.6802, [α]²⁰ _(D)=+140.4 (c=0.5, acetone).

Example 22

Preparation of the Catalyst Rh(6a)OAc₂:

Under a N₂ atmosphere, [RuPhC₂]₂ (25 mg, 0.05 mmol) and the ligand 6a(61 mg, 0.103 mmol) were added to a 10 mL one-neck flask, and then DMF(2 mL) were added. The reaction was continued at 100° C. for 3 h. Aftercooling to room temperature, 1.5 mL of a solution of anhydrous sodiumacetate (0.111 g, 1.3 mmol) in methanol was added. After 20 min,deoxygenated deionized water was added. A gray solid was precipitatedfrom the reaction system, and filtered out. The solvent and water wereremoved under reduced pressure to obtain the catalyst Rh(6a)OAc₂ (57 mg,yield=71%).

Example 23

Preparation of Catalyst Rh(6aXCF₃CO)₂:

Under a N₂ atmosphere, bis(2-methylallyl)-cycloocta-1,5-diene ruthenium(32 mg, 0.05 mmol) and the ligand 6a (61 mg, 0.103 mmol) were added to a10 mL one-neck flask, and then acetone (2 mL) were added. The reactionwas continued at 40° C. for 0.5 h. Then, trifluoroacetic acid (33 mg,0.3 mmol) was added and stirred overnight at 40° C. The solvent wasremoved under reduced pressure, and then petroleum ether (1 mL) wasadded, and filtered to obtain the target product Rh(6a)(CF₃CO)₂ (81 mg,yield=88%).

Example 24

Use of ligand 6a in the asymmetric hydrogenation of 2-methylcinnamicacid:

Under a N₂ atmosphere, 2-methylcinnamic acid (162 mg, 1 mmol), thecatalyst Rh(6a)OAc₂ (0.8 mg, 0.001 mmol) and methanol (1 mL) were addedto a hydrogenation vial.

After 12 h under a hydrogen atmosphere of 10 atm, the raw material wascompletely converted into a product. The product and aniline werecondensed to form an amide to measure the enantioselectivity of theproduct (ee>99%). HPLC conditions: Daicel ADH, volume of injection: 2 μL(c=1 mg/mL), IPA/hexane=90/10, 1.0 mL/Min, 210 nm, t_(R) (major)=26.8Min, t_(R) (minor)=29.7 Min.

The conversion rate of various substances in the presence of 6a is shownin FIG. 1.

The foregoing is a further detailed description of the present inventionin conjunction with specific preferred embodiments, and it should not beconsidered that the specific implementation of the present invention islimited thereto. Some simple deductions or replacements can be made bythose ordinarily skilled in the art to which the present inventionpertains without departing from the conception of the present invention,which are all regarded as falling within the protection scope of thepresent invention.

1. An oxa-spirodiphosphine ligand, having a structure of general Formula (I) below:

wherein in general Formula (I): R¹ and R² are independently alkyl, alkoxy, aryl, aryloxy, or hydrogen, in which R¹, R², R³ and R⁴ form a ring or do not form a ring; R⁵ and R⁸ are independently alkyl, aryl, or hydrogen; and R⁷, R⁸ are alkyl, benzyl, or aryl.
 2. The compound according to claim 1, wherein the oxa-spirodiphosphine ligand is (±)-oxa-spirodiphosphine ligand, (+)-oxa-spirodiphosphine ligand, or (−)-oxa-spirodiphosphine ligand.
 3. The compound according to claim 1, wherein the oxa-spirodiphosphine ligand is a compound having a structure below:

in which Ar is alkyl, benzyl or aryl.
 4. The compound according to claim 3, wherein Ar is phenyl, or phenyl substituted with alkyl or alkoxy.
 5. A method for synthesizing a compound according to claim 3, wherein the compound is obtained through a following route:


6. The compound according to claim 1, wherein the compound functions as a catalyst of reactions including hydrogenation reaction, hydroformylation reaction, hydrosilation reaction, hydroboration reaction, hydroxylation with hydrogen peroxide, hydroamination reaction, hydrocyanation reaction, isomerization and formylation reaction, hydroaminomethylation reaction, transfer hydrogenation reaction, allylation reaction, olefin metathesis reaction, cycloisomerization reaction, Diels-Alder reaction, asymmetric coupling reaction, Aldol reaction, Michael addition reaction, asymmetric epoxidation reaction, kinetic resolution and [m+n]cyclization reaction.
 7. (canceled)
 8. (canceled)
 9. The compound according to claim 1, wherein the compound functions as a catalyst of a following reaction, and wherein the reaction route is as follows:

wherein R=alkyl, fluoroalkyl or aryl.
 10. A diphosphine ruthenium acetate complex, which is a compound having a structure below:

wherein R=alkyl, fluoroalkyl or aryl.
 11. The diphosphine ruthenium acetate complex according to claim 10, wherein the diphosphine ruthenium acetate complex is prepared from the compound according to claim
 1. 12. The diphosphine ruthenium acetate complex according to claim 10, wherein diphosphine ruthenium acetate complex has a high activity and an enantioselectivity of greater than 99% for the hydrogenation of unsaturated carboxylic acids in organic solvents. 